Malignant tumor, as a vital disease threatening the human health, is the second leading cause of mortality. Statistics shows that the top 5 malignant cancers contributing to death in China are stomach cancer, liver cancer, lung cancer, esophagus cancer and large intestine cancer. Tumor is the abnormal hyperplasia of cell. Cancer cells have gained the ability of uncontrolled growth and reproduction, thereby invading adjacent normal tissue and metastasizing to distant tissues or organs. Tumorigenesis is a complex and gradual process with multiple factors and steps.
Carcinogenesis of normal cells is related to alter genetic characteristics. Generally, genes directly associated with cancer are often divided into two categories: (i) cancer-causing genes, called oncogenes, which are involved in cell growth, metabolism, promotion and regulation of cell proliferation and differentiation and (ii) cancer-inhibiting genes, called tumor suppressor genes, which are related to inhibition of neoplastic cell transformation and tumorigenesis. These two classes of genes are targets of the mutations that convert normal cells to cancer ones. Mutations including point mutation, loss or shift of DNA fragments of these two classes of genes can lead to uncontrolled cell growth and neoplasm.
Surgery, radiotherapy and chemotherapy have been the three main models of tumor therapy in recent years. These therapeutic methods are based on killing tumor cells directly, and it is difficult to completely eliminate all the cancer cells and is prone to injuring normal tissue, especially to impairing organism immune system and affecting native cellular immunity. With the development of modern molecular biology and genetic engineering technology, biological therapy has become the fourth model of tumor therapy. Deregulation of the dynamic balance, which exists between tumor and organism defense system under normal conditions, causes tumor proliferation and dissemination. Tumor biological therapy refers to the treatment of organism by regulating it's biological reaction according to tumor host defense mechanism or using biological reagent, which results in the tumor cell inhibition or death. Take tumor suppressor gene therapy for example, it restores the function of the tumor suppressor by transfer of tumor suppressor genes which are inactivated or absent in tumor cells, thereby exerting inhibitory or therapeutic effect on proliferation and metastasis of malignant tumor.
In order to effectively cure and prevent tumor, there is an urgent need in the art to provide more tumor suppressor proteins and associated activators/inhibitors.